The host-parasite relationship in experimental syphilis will be studied systematically with a particular focus on the role of immunity. Syphilis represents a major unsatisfactorily controlled endemic infectious disease with epidemic potential. The immune response to the infecting organisms, Treponema pallidum, is poorly understood. Our laboratory has been engaged in a basic study of the immune response of the rabbit for over ten years. The assays and understanding that has been developed will be applied to experimental T. pallidum infection in the rabbit. The immune system of rabbits with active infection, as well as rabbits resistant to T. pallidum re-infection, will be studied. The assays applied will include serologic tests for syphilis, T and B cell distribution, mitogenic response of lymphoid cells, tissue distribution of lesions and treponemes by fluorescence and immunoelectronmicroscopy, protective tests by passive local immunization, and effect of re-challenge. When the course of the experimental disease is fully characterized by these observations, the effect of infection in neonatal rabbits, cortisone treated rabbits and thymectomized rabbits will be studied. These studies should help define the effect of different immune states upon T. pallidum infection. The production of immunity to infection will be attempted using artificially prepared antigens, in particular, by using the "slime coat" component of T. pallidum. The late lesions of experimental syphilis will be determined by following the effects of infection over a 3-4 year period. It is anticipated that these studies will lead to new understanding of syphilis infection and provide insights that eventually can be applied to development of a clinically useful vaccine.